Findings from the first randomized controlled trial to date evaluating postpartum antiretroviral therapy (ART) for women with high CD4 cell counts (over 400 cells/mm3) highlight a critical need to increase treatment acceptance in this population, according to research presented at the 21st International AIDS Conference (AIDS 2016) last week in Durban.

Despite counseling and prior exposure to intense ART education and HIV monitoring within a highly-resourced clinical trial setting, over a third of women declined ART when the offer of treatment was extended to all women in the study, saying they needed more time to consider the benefits for their own health.

Effective implementation of the "treat all" approach recommended by the World Health Organization (WHO) requires addressing the significant challenges these findings raise.

The findings come from the Promoting Maternal and Infant Survival Everywhere (PROMISE 1077HS) study, carried out at 52 clinical research sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand, and the United States.

The study was conducted between January 2010 and November 2014 to determine if health over the long term is better served by continuing or stopping ART after delivery among non-breastfeeding women with high CD4 cell counts who did not meet local criteria for starting ART.

PROMISE 1066HS Results: Continued Postpartum Treatment

The PROMISE study found that continuing ART after giving birth was safe and associated with reduced illness and infection in over 1600 young asymptomatic women with high CD4 cell counts, Judith Currier told participants at the conference. Virological failure was high (23%) in this study and resistance testing suggested the need to improve adherence for the majority of participants.

PROMISE 1077HS examined the effects of ART on postpartum maternal health; 1077FF and 1077BF evaluated the effects of intrapartum and postpartum ART regimens on vertical HIV transmission, as well as the effects of ART on postpartum maternal health in settings with formula feeding (FF) or breastfeeding (BF).

Asymptomatic HIV-positive non-breastfeeding women with CD4 cell counts equal to or above 400 cells/mm3 before starting treatment who began ART during pregnancy were randomized up to 42 days after delivery to continue or stop ART.

Analyses reflect follow-up until July 2015. All participants were told about the findings of the START study and all were offered ART.

Among the 1652 women enrolled, the median age was 27 and 28 years in the continue (n=827) and stop (n=825) arms, respectively. At entry the median CD4 cell count was 696 cells/mm3 and 695 cells/mm3, respectively. Median ART exposure before delivery was 19 weeks, and 94% had a viral load under 1000 copies/mL.

After a median follow-up period of 2.3 years, continued ART did not significantly reduce the risk of death, AIDS-defining illness, or serious non-AIDS events. However, the risk of WHO stage 2 and 3 events was halved in those randomized to continue ART: 39 (2.02 per 100 person-years) and 80 (4.36 per 100 person-years) events, respectively (hazard ratio 0.47; p<0.001).

When the composite endpoint of death, AIDS-defining illness, or serious non-AIDS events and WHO Stage 2 and 3 events was analyzed, continued ART reduced the risk of reaching this endpoint by 44% (hazard ratio 0.56).

While toxicity rates in the continue arm were higher, the difference was not statistically significant.

Of the 827 women randomized to continue ART 189 (23%) had confirmed virological failure. 155 (82%) had virological testing and 103 (66%) had no evidence of drug resistance at the time of failure; of the 52 women with evidence of failure, 22 had resistance to one of the drugs in the failing regimen.

Currier concluded that in addition to supporting the use of continued ART for postpartum women (Option B+), interventions to improve adherence as well as studies to examine newer regimens with a high genetic barrier to resistance are needed to insure maximal long-term benefit.

Acceptance of Early ART

The PROMISE study followed women until June 2015, when all women in the study were offered the opportunity to begin immediate antiretroviral treatment in response to the results of the START study. START showed that early treatment reduced mortality and illness; its findings have led to the WHO recommendation of "treat all."

Despite these findings, Lynda Stranix-Chibanda, presenting on behalf of the IMPAACT/PROMISE trials, reported just over one-third of HIV-positive women when given the opportunity to start ART chose not to, notably after a single counseling session. They needed more time to consider the offer of starting ART for their own health. Stranix-Chibanda stressed the importance of this for program implementers in scaling up test-and-treat strategies.

Following the release of the START results, the PROMISE study team let active participants know of the findings, strongly encouraging those not on ART to start treatment immediately to optimize their own health. Starting treatment carried no financial cost nor did the decision affect continued participation in the studies.

Stranix-Chibanda presented a summary of the participants’ responses and their reasons for accepting or declining early ART.

A mixed methods approach was used to collect responses from participants getting the START information. Staff contacted participants asking them to return to the clinic. Using a structured script, START results were given and the women's understanding assessed. During a client-centered counseling session, those not on ART were advised to accept the offer to start treatment. Women chose their primary reason for accepting or declining the offer of early ART from a set of closed options.

Of the 1483 (35%) women not on ART and advised to start, 984 (66%) accepted and just over a third 499 (34%) declined. Acceptance rates varied among the 14 countries, ranging from a maximum of 100%, a mean of 66%, and a minimum of 37%.

Reasons given for declining ART (1077BF/FF and 1077HS) included wanting more time to consider (44% and 33%, respectively) and feeling well and knowing they had a high CD4 cell count (13% and18%, respectively). Among those accepting early ART, 46% and 43%, respectively, did so because of health concerns, while 35% and 36% did because of the protocol team’s recommendation.

With continued counseling, however, the proportion of women who remain off ART decreases with each visit, supporting the important need for more time to consider treatment.